We propose to develop a noninvasive, room-temperature transcutaneous gas sensor based on the nano-structured metal oxides as a rapid medical diagnostic. In Phase I, we successfully demonstrated the application of a titania nanotube-based hydrogen sensor to monitor transcutaneous hydrogen levels for predicting lactose intolerance in volunteer patients. In Phase II, we will develop a hydrogen and carbon dioxide (H2-CO2) sensor array for simultaneously detecting transcutaneous H2 and CO2 levels. Measurement of the transcutaneous gases will be used for detecting possible acidosis and necrotizing enterocolitis (NEC). The specific objectives of this Phase II project are {1} to design a standalone, self-contained sensor reader and {2} to miniaturize and repackage the new sensor reader into a watch-like device. We will also {3} continue to fabricate and improve the titania H2 sensing elements, as well as {4-5} fabricate and improve the performance of a nanoporous CuO-WO3 film for CO2 sensing. Upon completing the sensing elements, we will {6} develop an algorithm to determine the actual transcutaneous H2 and CO2 levels based on the sensor responses. To test the performance of the sensor system, we will first {7} correlate the transcutaneous H2 levels to exhaled breath H2 and the transcutaneous CO2 to blood CO2. We will then {8} measure the transcutaneous H2 and CO2 on preterm and full term infants with documented NEC/acidosis and suspected NEC/acidosis. Finally, we will {9} measure the transcutaneous gases on the test subjects with confirmed NEC/acidosis during the treatment and recovery phases. This Phase II project will involve scientists and engineers from SentechBiomed Corporation and James Kendig, M.D., of the Penn State Children's Hospital at Hershey Medical Center. The primary role of SentechBiomed is to fabricate the new sensor readers, the gas sensing elements, and establish a calibration algorithm, as well as analyze the clinical research data for sensor measurement calibration. Dr. Kendig at the Hershey Medical Center will conduct clinical research to evaluate the performance of the sensor and collect crucial clinical data for analysis. The outcome of this work is a noninvasive, real time sensor system for detecting certain diseases that can be diagnosed by monitoring the variation in excreted transcutaneous gases. Such a sensor system could prove to be of tremendous utility for improving early diagnosis, and hence care management, of diseases such as acidosis and necrotizing enterocolitis.